单次口服莫达芬尼片在中国健康志愿者的药代动力学  

Pharmacokinetics of modafinil tablets after a single oral dose in Chinese healthy volunteers

作　　者：王睿[1] 方翼[1] 周筱青[1] 柴栋[1] 王中孝[1] 王林[2] 金义光[2] 彭涛[2] 

机构地区：[1]解放军总医院药材处,北京100853 [2]军事医学科学院放射医学研究所,北京100850

出　　处：《中国临床药理学杂志》2004年第4期278-282,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究单次口服莫达芬尼片的药代动力学。方法选择9名健康成年男性受试者分别单次口服100,200,300mg 3个剂量的莫达芬尼片后,用HPLC法测定血中原形药莫达芬尼及代谢产物莫达芬尼酸浓度,用3P97软件进行数据处理,计算药代动力学参数。结果原形药莫达芬尼的药-时曲线符合二房室模型,其主要药代动力学参数的Cmax、AUC0-∞、AUC0-t随剂量加大而增加;t1/2b、tmax、b、CL与给药剂量无关。莫达芬尼片原形药经肾排泄较少,48h经肾累积排泄率分别为(4.44±4.28)%,(3.35±2.20)%和(2.86±1.39)%。主要代谢产物莫达芬尼酸药-时曲线符合二房室模型,48h莫达芬尼酸经肾累积排泄率分别为(33.51±18.90)%,(32.36±19.92)%和(22.88±6.89)%。结论莫达芬尼在100～300mg内,呈线性动力学特征而无饱和性,其消除过程是经肝脏代谢,代谢产物为莫达芬尼酸,代谢产物主要经肾排泄。Objective To investigate the pharmacokinetics of modafinil tablets afteroral single dose in Chinese healthy volunteers. Methods The drug and the metabolite(modafinil acid)concentrations of plasma sample from the 9 volunteers after taking100,200,300mg modafinil tablets were determined by HPLC method, and thepharmacokinetic parameters were calculated by 3P97 software. Results The plasmaconcentration -time curve of modafinil fit two compartment model after oral 100,200,300mg, and the Cmax、AUC0~∞ increased with dose rising. There was nosignificant difference in pharmacokinetic parameters tmax, t1/2b,Vd, CL betweenthe three groups. The cumulative excretion rate of modafinil in urine in 48h were(4.44±4.28)%,(3.35±2.20)% and (2.86±1.39)%. The plasma concentration-time curve of modafinil acid fit two compartment model, the cumulative excretionrate of modafinil acid in urine in 48h were(33.51±18.90)%,(32.36±19.92)% and(22.88±6.89)%, respectively. Conclusion The plasma concentration -time curvefit two compartment model after an oral dose of modafinil, most of modafinil istransformed to modafinil acid in liver, and the metabolite mainly excreted throughkidney.

关 键 词：莫达芬尼 莫达芬尼酸 高效液相色谱法 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R971.7[医药卫生—药学]